exploiting nature’s toolbox - · pdf filefow kam loon nus p.h.d. student ... industry...

For Production of Chiral Fine ChemicalsFor Production of Chiral Fine Chemicals
Exploiting NatureExploiting Natures Toolboxs Toolbox

Current Programme ManpowerUndergraduate Students
Chief Executive Officer, CEOSim Siang Tze Victor
NUS Applied Chemistry Undergraduate
Graduate Student
Chief Scientific Officer, CSOFow Kam Loon NUS P.H.D. student

Current Programme Manpower
Undergraduate Students
Head, Downstream ProcessHead, Human ResourceWon Jun YiNUS Applied Chemistry Undergraduate
Head, Upstream Process and ProductionHead, Marketing Jian Ming XianNUS Applied Chemistry Undergraduate
? Chief Financial OfficerN.N (To be elected)

Current Programme Manpower
Head, Overseas LiaisonLester PoonUniversity of British Columbia Biochemistry Undergraduate

Scientific Advisory Board
Prof. Dr. Christian Wandrey (Co-initiator of 6 start-ups) (Invited)Guest Professor, NUS Applied Chemistry ProgrammeUniversity of Bonn, Germany Chairman, Department of Biotechnology 2 at the Research Center (FZ) Jlich, Germany
Assoc. Prof. Dr. Jaenicke Stephan (Chairman)Head, NUS Applied Chemistry Programme
Dr. Ivy Tan (Ciba Specialty Chemicals, Singapore) (Invited)P.H.D. Biological Engineering (Germany)M.Sc. Chemical Engineering (United Kingdom)B.Sc. Chemical Engineering (Singapore)

Biotechnology
MultidisciplinaryMultidisciplinary

Current Process Development
This is categorized into 2 processes.
Biochemical Production processes (Synthesis of Chiral Chemicals)
Downstream processes (Automation and Prototypes)

Current ProductionProduction Process
Our present product of Ethyl (S)-3-hydroxybutyrate is >98% optical purity (Enantiomer Excess).
Currently we have fine tuned the purification process to >99% purity.
Monetary aspects of our process using Bakers Yeast as compared to Jlich Chiral Solutions Alcohol Dehydrogenase.(Both enzymatic and whole cells methods are feasible to start on)
Targeting companies that produces and/or companies requiring Active Pharmaceutical Ingredients (APIs) such as Pfizer, GSK, LonzaLonza GroupGroup, Jlich Chiral Solutions (wholly-owned subsidiary of CodexiCodexis) etc.

ProductSubstrate Yield (%)EnantiomericExcess (%)
57-67 84-87
58 90
Some products reduced by Bakers Yeast are used as important intermediate for the synthesis of some FDA approved HIV-1-protease inhibitors
59 >97
10056 >98.5%
Possible Microorganisms Projects (Bakers Yeast Reduction)

Production of Ethyl (R)-3-hydroxybutyrate by ADH LB
ee > 99.8%
Speciality Chemicals Magazine, 2004, Vol. 24 (4), 39-40.
Prices:
< 1000 Euro/Kg for 50 kg
< 500 Euro/kg for 200 kg
< 50 Euro/kg for tonne scale
O
O OLB-ADH
NADPH +H+ NADP+
O
LB-ADH
OH
(R) O
OHHO
Process Data:
Educt conc. 500 mM (66 g/L)
Conversion >99%
NADP conc. 0.05 mM
Possible Enzymatic Project (ADH LB Reduction)

Potential IndustryIndustry Collaborations
Lonza Group & Bio*One Capital Joint Venture16 August 2005 (Newsroom, Biomed Singapore News)Building of Four mammalian bioreactor trains each with capacity of up to 20'000 litres by 2008.
5 December 2006 (Newsroom, Biomed Singapore News)US $350 million large-scale mammalian cell culture facility built in Singapore for the manufacture of commercial biopharmaceuticals by 2011.
Codexis Inc25 August 2006 (The Business Times by Chen Huifen) US $40 million R&D center in Singapore to supply technology and active pharmaceutical ingredients (API) for drug companies

Automation/Integration with BIOSTAT CLab-scale fermentation system
- Cost Effectiveness, Better Yield and Avoiding Product Inhibitor
Membrane filtration systemReplaces Centrifuging Technique an increase in yield and decrease in processing time
Current DownstreamDownstream Process
Potential Project

Useful concept for membrane filtration with automated backwashing- Membrane Filtration with Automated Backwashing
BIOSTAT C + Filtration System
In-Situ Product Recovery- Integrated downstream processing:
Current DownstreamDownstream Process
In Progress To be Executed

Innovative Programme
1. Acting as a platform to create solutions through Research & Development to address clients needs with respect to speed, costand risk.
2. Creating a whole process development that includes the research,development, scale-up, engineering design, and economic analyses up to pilot scale production. (One Stop Shopping)
3. Comprises of Biochemical Production processes (Synthesis of Chiral chemicals) and Downstream processes (Automation and Prototypes)
4. Main focus is to create synergy between academic institutions and industry (faster time to market) for process development of fine chemicals.

Differences between NUS-Industry Collaboration Laboratory and Innovative Programme
Low cost involved in personnel and equipment except for a nominal grant to cover purchasing of chemicals purchase and maintenances of equipment.
More development oriented of bringing research to actual pilot plant scale manufacturing capabilities.
Promoting leadership among students.
Enhancing innovation to help industry in a more efficient manner.
Innovative Programme: Providing low cost development process that promotes entrepreneurship and enhances innovation

What we can offer to the industry?
Tap into multidisciplinary human resources in the whole of NUS.
Underutilized Capital Intensive equipments availability in laboratories.
Minimal cost involved for clients except for a reasonable research grant. (Projects are based on performance, employees are rewarded with both monetary and non-monetary benefits upon successful projects)
Significant cost savings rather than client doing in house. (Most companies are preoccupied with production optimization but no resources for independent product development)

Huge Skilled Labour Costs
Writing Successful Proposals by Professor Steven L. Bernasek, Program Officer at National Science Foundation
~ 40%!

Specialized Human Resources
3 main groups of employeesProfessors acting as NonNon--Executive DirectorsExecutive Directors(Job Scope is Project Approval and assisting in Industry Liaison)Graduate Students acting as Project ManagerProject Manager(Job Scope is Professional Guidance and Supervision of Projects)Undergraduates acting as Project OfficersProject Officers(Job Scope is Industry Liaison, Process Development with Innovation and Economical Analysis)New recruitment every 6-12 months,1 month transition period
The people are the key to success!The people are the key to success!

Business Model OutlineHow are the projects carried out?
1. Innovative Programme directors identify a need for whole/partial process development and cater to the industry. (Technology Push)
OR
2. Clients have a need for whole/partial process development and delegate a project to Innovative Programme directors. (Market Pull)

Programme Model Outline
Director (Professor)
Mentor (Graduate Students)
Process Development (Optimization and Pilot Plant Sale)
Sales
Potential ClientsProjects
Feasibility
Project Requirements
Guidance
Follo
w U
p / P
ropo
se P
roje
cts

Attractiveness of Innovative Programme
Programme Benefits
Non-Monetary Benefits (Main Push Factor)
Monetary Benefits (Bonus) To be introduced later.
http://numerovertassociatif.blogs.com/.shared/image.html?/photos/uncategorized/motivation.jpg

Non-Monetary Benefits
Everyone BenefitsNational University of Singapore & Faculty of ScienceProfessorsGraduate StudentsUndergraduate StudentsOutside Industry

National University of Singapore &Faculty of Science
Fulfill NUS commitment to create education that transforms.An innovative programme that educates students in a controlled simulated industry set up.Niche programme to groom students leadership spirit.Enhancing future potential collaborationsbetween interdisciplinary facultiesinterdisciplinary faculties to create a true NUS team as well as between industry and industry and academic institutionsacademic institutions.

Professors
Provides an alternative teaching career pathRecognition taken in grooming students and promoting entrepreneurshipEnhances the reputation of professorsDouble chances of research paper publicationsPaves the way for future multi disciplinary collaboration (Engineering and Chemistry etc.)

Graduate Students
Personalized testimonial from ProfessorsOpportunity for research and development and working at the same timeFast track real time industry exposure to supervisory and project management rolesupervisory and project management roleFulfilling 50% of teaching assistant requirements(Subject to FOS approval for MOEs Teaching Criteria)

Personalized testimonials from ProfessorsAlternative learning moduleAlternative learning module to UROPSHands-On exposure to entrepreneurship through economical analysis and the multi disciplinary problems faced in scale up operationsWorking i

exploiting nature’s toolbox - · pdf filefow kam loon nus p.h.d. student ... industry...

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